USPTO Patents Application 09978191

United States Patent and Trademark Office

UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450

Alexandria, Virginia 22313-1450
www.uspto.gov

APPLICATION NO.

FILING DATE

FIRST NAMED INVENTOR

ATTORNEY DOCKET NO.

CONFIRMATION NO.

09/978,191

10/15/2001

Audrey Goddard

35489 7590 07/17/2007

HELLER EHRMAN LLP
275 MIDDLEFIELD ROAD
MENLO PARK, CA 94025-3506

GNE.2630P1C4

4728

EXAMINER

O HARA, EILEEN B

ART UNIT

1646

PAPER NUMBER

MAIL DATE

DELIVERY MODE

07/17/2007 PAPER

Please And below and/or attached an Office communication concerning this application or proceeding.

The time period for reply, if any, is set in the attached communication.

PTOL-90A (Rev. 04/07)

Office Action Summary

Application No.

09/978,191

Applicant(s)

GODDARD ET AL

CAaminui

Eileen B. O'Hara

Art Unit

1646

- The MAILING DATE of this communication appears on the cover sheet with the correspondence address -
Period for Reply

A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.

- Extensions of time may be available under the provisions of 37 CFR 1 .136(a). In no event, however, may a reply be timely filed
after SIX (6) MONTHS from the mailing date of this communication.

- If NO period for reply is specified above, the maximum statutory period will apply and wilt expire SIX (6) MONTHS from the mailing date of this communication.

- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 1 33).
Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
earned patent term adjustment. See 37 CFR 1 .704(b). ,

Status

1 )S Responsive to communication(s) filed on 07 June 2007 .
2a)n This action is FINAL. 2b)S This action is non-final.

3) n Since this application is in condition for allowance except for formal matters, prosecution as to the merits is

closed in accordance with the practice under Ex parte Quayle, 1935 CD. 11, 453 O.G. 213.

Disposition of Claims

4) ^ Claim(s) 63.69 and 70 is/are pending in the application.

4a) Of the above claim(s) is/are withdrawn from consideration.

5) Q Claim(s) is/are allowed.

6) [3 Claim(s) 63. 69 and 70 is/are rejected.

7) D Claim(s) is/are objected to.

8) D Claim(s) are subject to restriction and/or election requirement.

Application Papers

£))□ The specification is objected to by the Examiner.

10)D The drawing(s) filed on is/are: a)D accepted or b)D objected to by the Examiner.

Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1 .85(a).

Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
1 1 )□ The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-1 52.

Priority under 35 U.S.C. § 1 1 9

12)D Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 1 19(a)-(d) or (f).
a)D All b)Q Some * c)D None of:

1 .□ Certified copies of the priority documents have been received.

2. D Certified copies of the priority documents have been received in Application No. .

3. Q Copies of the certified copies of the priority documents have been received in this National Stage

application from the International Bureau (PCT Rule 17.2(a)).
* See the attached detailed Office action for a list of the certified copies not received.

Attachment(s)

1 ) S Notice of References Cited (PTO-892) 4) □ Interview Summary (PTO-413)

2) □ Notice of Draftsperson's Patent Drawing Review (PTO-948) Paper No(s)/Mail Date. .

3) □ Information Disclosure Statement(s) (PTO/SB/08) 5) □ Notice of Informal Patent Application

Paper No(s)/Mail Date . 6) □ Other: .

U.S. Patent and Trademark Office
PTOL>326 (Rev. 08-06)

Office Action Summary

Part of Paper No./Mail Date 20070714

Application/Control Number: 09/978,191 Page 2

Art Unit: 1646

Claims
Withdrawal of Finality

1 . Upon further consideration, the finality of the last office action is withdrawn.

Claims Status

2. Claims 63 and 69-70 are pending in the instant application. Claims 58-62 have been
canceled as requested by Applicant in the Paper filed June 7, 2007.

Withdrawn Rejections

3. The rejection of claims under 1 12 § 1 for lack of written description is withdrawn in view
of Applicants' amendment.

Claim Rejections - 35 USC § 101 and §112
35 U.S.C. 101 and 1 12, first paragraphs read as follows:

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or
any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and
requirements of this title.

The specification shall contain a written description of the invention, and of the manner and process of making
and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it
pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode
contemplated by the inventor of carrying out his invention.

4. Upon further consideration, claims 63, 69 and 70 are rejected under 35 U.S.C. 101 and
1 12, first paragraph, because the claimed invention is not supported by either a specific and
substantial asserted utility or a well established utility, for reasons of record in the previous

office actions.

Application/Control Number: 09/978,191 Page 3

Art Unit: 1646

Claims 63, 69 and 70 are also rejected under 35 U.S.C. 112, first paragraph. Specifically,
since the claimed invention is not supported by either a credible, specific and substantial asserted
utility or a well established utility for the reasons set forth above, one skilled in the art clearly
would not know how to use the claimed invention.

Applicant relies on the gene amplification data for the gene encoding PR0213-1
polypeptide for patentable utility of the PR0213-1 polypeptide. The gene amplification assay
> provides a patentable utility for the PR0213-1 nucleic acid. However, the instant application has
claims directed to PR0213-1 protein. The Polakis and Scott declarations submitted previously,
that changes in level of mRNA correlates with changes in protein abundance, have been found
persuasive by the Examiner. Therefore, the only issue remaining is whether gene amplification
correlates with increased transcription and mRNA levels. The art establishes that there is no
strong correlation between gene amplification and increased mRNA. Indeed, given the
disclosure in the art, such as Pennica et al., Godbout et al. and and Li et al., of record, that there
is not always such a correlation, the skilled artisan would not assume it is so, but would perform
the experiment to verify it.

Li et al., Oncogene, Vol. 25, pages 2628-2635, 2006. Li et al. used a functional approach
that integrated simultaneous genomic and transcript microarray, proteomics, and tissue
microarray analyses to directly identify putative oncogenes in lung adenocarcinoma. On page
2633, right column, Li et al. state: "In our study, 68.8% of the genes showing over-
representation in the genome did not show elevated transcript levels, implying that at least some
of these genes are 'passenger 1 genes that are concurrently amplified because of their location with

Application/Control Number: 09/978,191 Page 4

Art Unit: 1646

respect to amplicons but lack biological relevance in terms of the development of lung
adenocarcinoma"

A slight amplification of a gene does not necessarily mean overexpression in a cancer
tissue, but can merely be an indication that the cancer tissue is aneuploid. The preliminary data
were not supported by analysis of mRNA or protein expression, for example. Also, the literature
reports that it does not necessarily follow that an increase in gene copy number results in
increased gene expression and increased polypeptide expression, such that the claimed
polypeptides would be useful for diagnosis of cancer or as a drug target. For example, Pennica et
al. (1998, PNAS USA 95:14717-14722) disclose that:

"An analysis of WISP- 1 gene amplification and expression in human colon tumors showed a
correlation between DNA amplification and overexpression, whereas overexpression of WISP-3
RNA was seen in the absence of DNA amplification. In contrast, WISP-2 DNA was amplified in
the colon tumors, but its mRNA'expression was significantly reduced in the majority of tumors
compared with the expression in normal colonic mucosa from the same patient."
See p. 14722, second paragraph of left column; pp. 14720-14721, "Amplification and Aberrant
Expression of WISPs in Human Colon Tumors." Therefore, data pertaining to PR0213-1 nucleic
acids do not necessarily indicate anything significant regarding the claimed PR0213-1
polypeptides. Thus, the data do not support the implicit assertion that PR0213-1 can be used as a
cancer diagnostic. Significant further research would have been required of the skilled artisan to
determine whether PR0213-1 is overexpressed in any cancer to the extent that it could be used
as a cancer diagnostic, and thus the implicitly asserted utility is not substantial.

Application/Control Number: 09/978, 1 9 1 Page 5

Art Unit: 1646

The abstract of Godbout teaches "The DEAD box gene, DDX1, is a putative RNA
helicase that is co-amplified with MYCN in a subset of retinoblastoma (RB) and neuroblastoma
(NB) tumors and cell lines. Although gene amplification usually involves hundreds to thousands
of kilobase pairs of DNA, a number of studies suggest that co-amplified genes are only
overexpressed if they provide a selective advantage to the cells in which they are amplified."
The protein encoded by the DDX gene had been characterized as being a putative RNA helicase,
a type of enzyme that would be expected to confer a selective advantage to the cells in which it
(the DDX gene) was amplified. On page 21167, right column, first full paragraph, Godbout et
al. state "It is generally accepted that co-amplified genes are not over-expressed unless they
provide a selective growth advantage to the cell (48, 49). For example, although ERBA is
closely linked to ERBB2 in breast cancer and both genes are commonly amplified in these
tumors, ERBA is not overexpressed (48). Similarly, three genes mapping to 12ql3-14 (CDK4,
SAS and MDM2) are overexpressed in a high percentage of malignant gliomas showing
amplification of this chromosomal region, while other genes mapping to this region (GADD153,
GL1, and A2MR) are rarely overexpressed in gene-amplified malignant gliomas (50, 51). The
first three genes are probably the main targets of the amplification process, while the latter three
genes are probably incidentally included in the amplicons."

On the contrary, there is no structure/function analysis in the specification regarding the
putative protein encoded by the PR0213-1 gene. It is not disclosed, and based upon the
sequence searches in this case, the Examiner can not find any reason to suspect, that the protein
encoded by the PR0213-1 gene would confer any selective advantage on a cell expressing it. It
has no known homology to an RNA helicase or any other protein that would be expected to

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Art Unit: 1646

confer a selective advantage to a tumor cell. Further, it cannot be determined from the abstract
whether the level of genomic amplification of the DDX1 gene was comparable to that disclosed
forPR0213-L

See also Konopka (Proc. Natl. Acad. Sci. (1986) 83:4049-4052), who state that "Protein
expression is not related to amplification of the abl gene but to variation in the level of bcr-abl
mRNA produced from a single Phi template" (see abstract).

In summary, it is clear that amplification of the genome more often than not does not
result in increased mRNA expression.

Therefore, the Examiner maintains that Applicant's measurement of an increase of

PR0213-1 genomic DNA does not support increased mRNA expression. Therefore, the

specification and cited references do not provide a specific and substantial utility for the encoded

protein. Further research needs to be done to determine whether the purported increase in

PR0213-1 DNA supports a role for the peptide in the cancerous tissue; such a role has not been

suggested by the instant disclosure. Such further research requirements make it clear that the

asserted utility is not yet in currently available form, i.e., it is not substantial. This further

experimentation is part of the act of invention and until it has been undertaken, Applicant's

claimed invention is incomplete. As discussed in Brenner v. Manson, (1966, 383 U.S. 519, 148

USPQ 689), the court held that:

"The basic quid pro quo contemplated by the Constitution and the Congress for granting
a patent monopoly is the benefit derived by the public from an invention with substantial
utility", "[ujnless and until a process is refined and developed to this point-where specific
benefit exists in currently available form-there is insufficient justification for permitting
an applicant to engross what may prove to be a broad field", and, "a patent is not a
hunting license", "[i]t is not a reward for the search, but compensation for its successful
conclusion."

Application/Control Number: 09/978,191
Art Unit: 1646

Page 7

Accordingly, the specification's assertions that the PR0213-1 polypeptides have utility in the
fields of cancer diagnostics is not substantial.

Conclusion

5. No claim is allowed.

Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Eileen B. O'Hara, whose telephone number is (571) 272-0878.
The examiner can normally be reached on Monday through Friday from 10:00 AM to 6:30 PM.

If attempts to reach the examiner by telephone are unsuccessful, the examiner's
supervisor, Gary Nichol can be reached at (571) 272-0835.

The fax phone number for the organization where this application or proceeding is
assigned is 571-273-8300.

Any inquiry of a general nature or relating to the status of this application should be
directed to the Group receptionist whose telephone number is (571) 272-1600.

Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications
may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
applications is available through Private PAIR only. For more information about the PAIR
system, see http://portal.uspto.gov/external/portal/pair. Should you have questions on access to

Application/Control Number: 09/978, 191 Page 8

Art Unit: 1646

the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll
free).

Eileen B. O'Hara, Ph.D.

Patent Examiner

EILEEN B. O'HARA
PR/MARY EXAMINER